Are sham-operated mice a valid comparator in studies using a bladder outlet obstruction model? A pitfall reveals a meaningful insight.

OBJECTIVE: To evaluate voiding behavior characteristics in intact and sham mice, and to examine whether intact mice show changes in "normal" micturition with aging. METHODS: A total of 72 8-week-old mice were divided into two groups - intact and sham - and the latter group was subjected to a sham of partial bladder outlet obstruction surgery. Urination frequency was evaluated (through metabolic cages) at 1, 2, 3, 6 and 12 months after the surgery (or at the equivalent time points for the intact mice). To address possible mechanisms for aging and surgical effects on urinary behavior, quantitative real-time polymerase chain reaction assays were carried out. Primary data were evaluated using scatter plots and descriptive statistics. RESULTS: In sham mice, urination frequency showed strong variation at the earlier post-surgical time points (especially at 1 month), with variation decreasing with time. Quantitative real-time polymerase chain reaction showed that the serotonin 2C receptor-encoding mRNA accumulated to >28-fold higher levels at 24 months compared with 3 months in intact mice. A major limitation of the quantitative real-time polymerase chain reaction experiments was that we did not separate whole bladder into muscle and mucosa. CONCLUSIONS: Although a sham operation is typically used in partial bladder outlet obstruction experiments to provide control animals, the sham group might itself show increased variation in micturition frequency at early times after surgery, compared with intact animals.

Long-term administration of alpha-1 blocker can reverse the micturition pattern in a bladder outlet obstruction murine model.

OBJECTIVE: To investigate the effect of chronic administration of an alpha-1 blocker on micturition patterns in long-term partial bladder outlet obstruction. METHODS: Mice were divided into three groups: a normal group, in which animals were fed a standard diet; a partial bladder outlet obstruction group, in which the proximal urethra was tied and animals were fed a standard diet; and a partial bladder outlet obstruction + naftopidil group, in which the proximal urethra was tied and animals were fed a standard diet containing naftopidil. Micturition behavior was evaluated in all groups for 6 months after partial bladder outlet obstruction surgery. The parameters evaluated included voided volume, time per void, urination frequency and total urine volume. Quantitative assessment of gene expression was also carried out. RESULTS: Total urine volume, as well as total and average voided volume during night, was significantly decreased in partial bladder outlet obstruction + naftopidil mice compared with partial bladder outlet obstruction animals. The levels of transcripts encoding 5-hydroxytryptamine 2A and tissue inhibitor of metalloproteinase 2 were significantly decreased in the partial bladder outlet obstruction + naftopidil group compared with the partial bladder outlet obstruction group. CONCLUSIONS: Long-term administration of an alpha-1 blocker seems to reverse the disturbance of the micturition pattern caused by partial bladder outlet obstruction. Mechanistically, this effect might be mediated by changes in the expression of a serotonin receptor and/or in the activity of the fibrogenesis pathway.